Challenge Yourself with Something New

There has been an explosion of medical information lately that is destined to influence the content of the USMLE. The exam is not only getting harder but there is important emphasis on recent advances and trending topics. Recent advances in Pharmacology is one critical area to become conversant with. Some drugs have such unique properties or attributes that one cannot help but predict their immediate relevance for the USMLE. In fact, you would be a fool not to prepare for something like this. 

In February 2020, the FDA approved the first orally disintegrating tablet for aborting migraines. We immediately brought our panel of USMLE question writers together to produce good USMLE questions on this concept before anybody heard such a therapy was available.

Check out one of our USMLE questions on these concepts. This is one of the questions written by our experts that our students that our students have to be able to answer during the USMLE Insider Prep Course for USMLE Step 1. Test yourself with this and let us see how you do. We will discuss the answer and offer explanations later. 

1. A 38-year-old woman is referred to a neurologist because of throbbing headaches. The headaches, which are are accompanied by nausea, anorexia and food intolerance, phonophobia, and photophobia are felt on the leftt frontotemporal region and occur with severe intensity. The pain typically lasts for about 8 hours and is worsened by climbing the stairs. She has experienced about 7 episodes this month. She reports that a visual phenomena, characterized by a band of absent vision with shimmering zigzag border, often precedes the headaches by 20 to 30 minutes. The physician decides to prescribe an orally disintegrating tablet for a rapid relief of symptoms. Which of the following agents is most likely to be given to this patient? 

A. Dihydroergotamine
B. Lasmiditan
C. Methysergide
D. Pizotifen
E. Rimegipant
F. Rizatriptan
G. Ubrogepant

Explanation:

The answer is E. Rimegipant is a highly potent, orally administered calcitonin gene-related peptide (CGRP) receptor antagonist. This is a small molecule inhibitor that binds to the receptor for CGRP, a peptide which is thought to be causally involved in migraine pathophysiology (by virtue of being a dilator of blood vessels in the brain). Inhibition of CGRP pathway disrupts the vasodilation and returns the vessels to their original size.

Rimegipant is indicated for acute treatment of migraine with or without aura. It was approved by the FDA in February 2020 and is the first CGRP receptor antagonist available in a fast-acting orally disintegrating tablet for the acute treatment of migraine in adults.

In clinical testing, a single 75-mg dose of rimegepant provided rapid migraine pain relief with patients returning to normal activities within 1 hour, with sustained benefit lasting up to 2 days in many patients. The majority of patients (86%) treated with a single dose did not need a migraine rescue medication within 24 hours.

(Choice A) Dihydroergotamine is available in intravenous, intramuscular, subcutaneous, and intranasal preparations. The intravenous route is used when more rapid results are desired. A dose of 1 mg intravenously every 8 hours with or without metoclopramide is safe and effective for treatment of status migrainosus.

(Choice B) Lasmiditan exerts its therapeutic effects for acute migraine through agonist effects at the 5-HT1F receptor. Lasmiditan is available for oral administration but it is not an orally disintegrating tablet.

(Choice C) Methysergide is an ergoline derivative that blocks 5-HT2A receptor and is used for migraine prevention therapy. It has fallen out of favor because of its association with retroperitoneal fibrosis.

(Choice D) Pizotifen is a serotonin antagonist acting mainly at the 5-HT2A and 5HT2C receptors. It is used for the prevention of migraine and cluster headache. 

(Choice F) Rizatriptan is a 5-HT1D agonist used for acute management of migraines. It is not available as an orally disintegrating tablet.

(Choice G) Ubrogepant and rimegipant are small molecule CGRP receptor antagonists indicated for acute treatment of migraine with or without aura. However, only rimegipant is available in orally disintegrating tablet formulation.